Oxidation of 9-alkylanthracenes by P450 2B1, horseradish peroxidase, and iron tetraphenylporphine iodosylbenzene systems: Anaerobic and aerobic mechanisms
Oxidation of 9-alkylanthracenes by P450 2B1, horseradish peroxidase, and iron tetraphenylporphine iodosylbenzene systems: Anaerobic and aerobic mechanisms
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DOI：
10.1021/bi952330f
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发表时间：
1996-02-27
期刊：
影响因子：
2.9
通讯作者：
Guengerich, FP
中科院分区：
文献类型：
--
作者：
Anzenbacher, P;Niwa, T;Guengerich, FP
研究了不同取代的烷基蒽作为多环烃氧化的模型；9-甲基蒽在几种体系中被氧化为9-（羟甲基）蒽、10-甲基-10-羟基-9-蒽酮和蒽醌，包括(i) NADPH-和O-2强化的大鼠肝微粒体，（ii）细胞色素P450 (P450) 2B1，由碘基苯（PhIO）或NADPH-P450还原酶、NADPH和O-2的混合物支持，（iii）辣根过氧化物酶和H2O2或过氧化乙酯，以及（iv）四苯基卟啉铁（FeTPP）和PhIO的混合物（在无水CH2Cl2/MeOH中）。微粒体系统也由9-甲基和9-乙基蒽形成二氢二醇。P450/NADPH/O-2体系生成的三种氧化产物均依赖于O-2，产物中加入了O-18(2)的标记，未加入(H2O)-O-18的标记。在FeTPP/PhIO系统中，这三个产品中没有纳入O-18(2)的标签。在辣根过氧化物酶/H2O2体系中，当O-2被省略时，这三种产物的生成减少，并且(H2O)-O-18和O-18(2)的标签都被加入到这三种产物中。结果可以用三种机制来解释。一种是由FeTPP和P450系统使用的，所有的氧转移都来自FeO实体。另外两种途径是由辣根过氧化物酶利用的，从自由基阳离子的形成开始，自由基阳离子可以与H2O或O-2反应，形成这里检测到的产物。9-甲基蒽自由基阳离子参与P450和FeTPP通路是一种可能性，但必须调用快速重排和氧反弹。比较不同的9-烷基蒽的产物并没有提供证据证明单电子氧化是这些化合物环氧化过程的一个组成部分。考虑了P450反应中缺乏(H2O)-O-18捕获自由基对DNA加合物形成的重要性。
Variously substituted alkylanthracenes were studied as models for polycyclic hydrocarbon oxidations; 9-Methylanthracene was oxidized to 9-(hydroxymethyl)anthracene, 10-methyl-10-hydroxy-9-anthrone, and anthraquinone in several systems, including (i) NADPH- and O-2-fortified rat liver microsomes, (ii) cytochrome P450 (P450) 2B1 supported by either iodosylbenzene (PhIO) or a mixture of NADPH-P450 reductase, NADPH, and O-2, (iii) horseradish peroxidase and either H2O2 or ethyl hydroperoxide, and (iv) a mixture of iron tetraphenylporphine (FeTPP) and PhIO (in anhydrous CH2Cl2/MeOH). The microsomal system also formed dihydrodiols from 9-methyl- and 9-ethylanthracenes. The formation of the three oxidized products by the P450/NADPH/O-2 system was dependent upon O-2, label from O-18(2) was incorporated into the products, and no label from (H2O)-O-18 was incorporated. No label from O-18(2) was incorporated into the three products in the FeTPP/PhIO system. In the horseradish peroxidase/H2O2 system, the formation of the three products was decreased when O-2 was omitted, and label from both (H2O)-O-18 and O-18(2) was incorporated into all three products. The results are interpreted in terms of three mechanisms. One is used by the FeTPP and P450 systems, with all oxygen transfers coming from an FeO entity. The other two pathways are utilized by horseradish peroxidase and begin with formation of a radical cation, which can undergo reactions either with H2O or with O-2 to form the products detected here. The involvement of a 9-methylanthracene radical cation in the P450 and FeTPP pathways is a possibility, but rapid rearrangement and oxygen rebound must be invoked. Comparisons of products from various 9-alkylanthracenes do not provide evidence that one-electron oxidation is an integral part of the epoxidation process with these compounds. The significance of the lack of trapping of' radical (by (H2O)-O-18) in the P450 reactions to DNA adduct formation is considered.